Clinical Evaluation of the CADence Device in Detection of Coronary Artery Diseases

Coronary Artery Disease Clinical Trial

— TURBULENCE  

Official title:

Pivotal Study of the CADence Device in Detection of Coronary Artery Diseases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01743040
• Other study ID #: 1038-001
• Status: Completed
• Start date: June 14, 2013
• Est. completion date: February 10, 2016

Study information

• Verified date: July 2020
• Source: AUM Cardiovascular, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a multi-center, prospective, non-randomized, double-blinded trial to evaluate the sensitivity and specificity of the CADence device in detecting the existence of clinically significant coronary artery disease as determined by either standard or CT angiography.

Description:

This is a multi-center, prospective, non-randomized, double-blinded, trial to evaluate the performance of the CADence in detecting the existence of at least one major coronary artery with clinically significant stenosis in a subject is defined as the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex , proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries.

Consented subjects will be evaluated with the CADence device and then undergo nuclear stress testing followed by either computed tomography or standard coronary angiography. The maximum expected timeframe between CADence and computed tomography Angiography or standard angiography is 6 weeks.

This is a double-blinded study. All physicians and subjects will be masked to the diagnostic results of the CADence until completion of CADence, nuclear stress, computed tomography or standard coronary angiogram testing for the subjects. Patient care will not be based on the CADence results.

Study participation will conclude after the computed tomography angiography or standard coronary angiography procedure.

computed tomograph or standard coronary angiography are considered acceptable clinical reference standards in this study and are gold standards for detection of coronary artery disease. The experimental unit of this study is the subject. Existence of clinically significant coronary artery disease in a subject is defined as the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries.

The study required sample size is 826 but may enroll up to 1,300 subjects. The sensitivity and specificity of the CADence are expected to be 80% and 73% respectively. Observed sensitivity and specificity will be compared to nuclear stress literature-based performance standards of 83% and 80% respectively using one sample non-inferiority binomial tests with a non-inferiority margin of 15 percentage points. Sample size requirements are 109 subjects with the presence of at least one lesion with ≥ ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left MAIN coronary arteries. to test the sensitivity hypothesis and 268 subjects without the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left MAIN coronary arteries. to test the specificity hypothesis. It was assumed that 15 percent of enrolled subjects would be found to have the presence of at least one lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left Main coronary arteries. In order to accrue 109 subjects with significant Coronary Artery Disease as defined in the protocol, 826 subjects must be enrolled. Sample sizes provide 85% power with alpha of 0.05 for each statistical test.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1014
• Est. completion date: February 10, 2016
• Est. primary completion date: February 10, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years and older

Eligibility

Subjects clinically indicated for nuclear stress test and who satisfy all the inclusion and exclusion criteria are eligible for participation.

Inclusion criteria:

Age 22 years or older Willing and able to give informed consent Clinical indication for nuclear stress test evaluation Chest pain syndrome

Two or more coronary artery disease risk factors as defined by:

1. Dyslipidemia: low-density lipoprotein (LDL) >130 mm/dL or high-density lipoprotein (HDL) <35 mm/dL or on treatment for dyslipidemia

2. Hypertension: blood pressure >140 millimeter of mercury (mmHg) systolic, >90 mmHg diastolic or on blood pressure altering treatment

3. Obesity: body mass index (BMI)>28

4. Current cigarette smoking

5. Diabetes: Type 1 or 2

6. Family history: coronary disease in a first or second degree relative

Exclusion criteria:

Body Mass Index (BMI)<18.5 or BMI >40

Known coronary disease as defined as:

Prior bypass surgery or coronary stenting Q-wave infarction on a past electrocardiogram (EKG) (>0.01 sec Q-wave duration in two adjacent leads)

Presence of pacemaker/defibrillator Presence of artificial valve Presence of obvious cyanotic or pre-diagnosed congenital heart defect and coarctation of the aorta Presence murmurs including valve lesions, ventricular septal defects, and arteriovenous (AV) fistulae.

Presence of moderate or severe valve disease as defined by >1/6 heart murmur on physical diagnosis Left Ventricular Assist Device (LVAD) Presence of scars on the site thorax areas Participation in trial within 30 days prior to collecting CADence data except participation in registry studies Asthma with wheezing Inability to lie flat in the supine position Acute coronary syndrome with elevated cardiac biomarkers (troponin (TP)>3x upper limit of normal (ULN) or creatine kinase MB (CKMB) >3x ULN) Heart Transplant Current cocaine use (within the past 24 hours, as reported by subject) Chronic Obstructive Pulmonary Disease (COPD) Contraindication to computed tomography (CT) angiography

• Renal failure with glomerular filtration rate (GFR)<50 (angio risk)

• Iodinated contrast allergy

• Elevated heart rate which cannot be controlled sufficiently to achieve a good computed tomography angiogram

• Body weight >350lbs.

• Sinus rhythm rate greater than 100 beats per minute at screening.

• Atrial fibrillation with average heart rate of greater than 70 beats per minute on resting screening electrocardiogram (ECG).

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Diagnostic Test:
• CADence
Patients with chest pain and two or more coronary risk factors and who were already indicated for nuclear stress test were enrolled in the study. The CADence was performed prior to nuclear stress test. Patients underwent standard angiogram based upon normal clinical judgement. In all other patients a CT angiogram followed. CADence is a handheld equipped with acoustic sensor technology, a patient booklet, remote algorithm and final report.

Locations

Country	Name	City	State
United States	MedStar Union Memorial Hospital	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Clearwater Cardiovascular	Clearwater	Florida
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Iowa Heart Center	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	North Ohio Research	Elyria	Ohio
United States	Hartford Hospital	Hartford	Connecticut
United States	Heart Center Research, LLC	Huntsville	Alabama
United States	Jackson Clinic	Jackson	Tennessee
United States	Lancaster General	Lancaster	Pennsylvania
United States	UCLA	Los Angeles	California
United States	Abbott/Minneapolis Heart Institute	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Cardiology Associates of Mobile	Mobile	Alabama
United States	Columbia University	New York	New York
United States	Mt. Sinai	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	CentraCare Heart & Vascular Center	Saint Cloud	Minnesota
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	HealthEast - St. Joseph's Hospital	Saint Paul	Minnesota
United States	United Heart and Vascular Clinic	Saint Paul	Minnesota
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AUM Cardiovascular, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity and Specificity of CADence to Detect Stenosis Relative to SPECT Performance, Using Either CT or Standard Angiogram as the Gold Standard	The CADence will be considered to have demonstrated effectiveness in detecting the presence of at least one lesion with = 70% diameter stenosis anywhere in the proximal Left anterior Descending (pLAD), mid Left anterior Descending (mLAD), proximal Left Circumflex (pLCx), mid Left Circumflex (mLCx), proximal Right Coronary Artery (pRCA), mid Right Coronary Artery (mRCA), distal Right Coronary Artery (dRCA) and Obtuse Margin 1 (OM1), Obtuse Margin 2 (OM2), and Ramus Intermedius (RI) if segment diameter >2.5 mm or =50% diameter stenosis in the Left Main coronary arteries if sensitivity and specificity are non-inferior within 15 percentage points to a sensitivity of 83% and a specificity of 80%, which is the literature-based Objective Performance Criteria (OPC) for nuclear stress tests.	No more than 3 weeks between CADence, SPECT and standard or CT angiogram